This application is a 371 of PCT/JP98/03776 filed Aug. 24, 1998.
The present invention relates to an ophthalmic composition for soft contact lenses (hereinafter to be abbreviated as SCL). More particularly, the present invention relates to a composition for enhancing the wettability of SCL, a method of enhancing the wettability of SCL and a method of inhibiting adsorption of terpenoid onto SCL.
SCL usually contains water and causes less uncomfortable feeling. However, a long-term use of the lens often causes a dry feeling. This is because when the water contained in the lens evaporates, precorneal tear film under SCL is affected and corneal stain occurs, and further, when the water content decreases, the curve of SCL and the like changes to have a different lens standard. As a result, an uncomfortable feeling is enhanced.
A dry feeling and an uncomfortable feeling due to lower water content are peculiar to SCL, and there is a demand for the solution to this problem of SCL.
It is therefore an object of the present invention to provide an ophthalmic composition for SCL, such as a composition capable of inhibiting a dry feeling, and an uncomfortable feeling caused by a decreased water content of SCL.
Another object of the present invention is to provide a method of enhancing the wettability of SCL.
The present inventors have conducted intensive studies in an attempt to achieve the above-mentioned objects and found that terpenoid can improve the wettability of SCL, thus inhibiting a decrease in the water content of SCL to eventually inhibit a dry feeling and an uncomfortable feeling, which resulted in the completion of the present invention.
Accordingly, the present invention provides the following.
(1) An ophthalmic composition for SCL, which contains a terpenoid as an active ingredient.
(2) The ophthalmic composition of (1) above, which is for enhancing the wettability of SCL.
(3) The ophthalmic composition of (1) or (2) above, wherein the terpenoid is at least one member selected from the group consisting of menthol, borneol and camphor.
(4) The ophthalmic composition of any of (1) to (3) above, which is in the form of an eye drop.
(5) The ophthalmic composition of any of (1) to (4) above, which contains polyoxyethylene sorbitan ester and which is in the form of a liquid when in use.
(6) The ophthalmic composition of any of (1) to (5) above, which is in the form of a liquid having a pH of not less than 5.5 when in use.
(7) A method of enhancing the wettability of SCL, which comprises bringing a terpenoid into contact with the SCL.
(8) The method of (7) above, wherein the terpenoid is at least one member selected from the group consisting of menthol, borneol and camphor.
(9) A method of inhibiting adsorption of terpenoid onto SCL, which comprises adding polyoxyethylene sorbitan ester to an ophthalmic composition which contains a terpenoid and which is in the form of a liquid when in use.
(10) A method of inhibiting adsorption of terpenoid onto SCL, which comprises adjusting a pH of an ophthalmic composition which contains a terpenoid and which is in the form of a liquid when in use, to not less than 5.5.
(11) The method of inhibiting adsorption of terpenoid onto SCL of (9) or (10) above, wherein the terpenoid is at least one member selected from the group consisting of menthol, borneol and camphor.
The terpenoid to be contained in the ophthalmic composition for SCL of the present invention may be a monoterepene such as menthol, borneol, camphor, geraniol, cineole, anethol, limonene, eugenol and the like, a sesquiterpene such as farnesol, nerolidol and the like, a diterpene such as phytol, cembrene and the like, or other terpenoid. Particularly preferred are menthol, borneol, camphor and the like.
The content of the terpenoid to be contained in the ophthalmic composition for SCL of the present invention is 0.0001-0.2 (W/V) %, preferably 0.001-0.05 (W/V) %, when in use.
The ophthalmic composition for SCL of the present invention, which contains a terpenoid, can be used as a composition for any ophthalmic use for SCL. To be specific, it can be used as a composition for enhancing the wettability of SCL, and the like.
The ophthalmic composition for SCL of the present invention can be used in any form of a preparation generally used for topical application to the eye. For example, it may be prepared into an eye drop, eye ointment, gel, solid preparation that becomes a liquid upon dissolution when in use (e.g., tablet, powder, granule, freeze-dry preparation and the like), and the like, with preference given to use in the form of an eye drop. The eye drop may be aqueous or non-aqueous, and may be a solution or suspension.
The SCL worn on an eye is washed with a tear fluid. Even if an ingredient of the ophthalmic composition is adsorbed onto SCL, it is normally washed away and rarely causes irritation to the eye, and the like. However, the adsorption of each ingredient is desirably as small as possible.
From this viewpoint, the present inventors have conducted various studies and found that (1) addition of polyoxyethylene sorbitan ester to an ophthalmic composition for SCL, which contains a terpenoid as an active ingredient, and which becomes a liquid upon dissolution when in use, and/or (2) adjustment of pH to not less than 5.5 when in use result(s) in the inhibition of adsorption of terpenoid onto SCL.
Accordingly, the present invention relates to an ophthalmic composition for SCL, which contains a terpenoid as an active ingredient and which becomes a liquid upon dissolution when in use, and provides
(1) a composition containing polyoxyethylene sorbitan ester and/or
(2) a composition having a pH of not less than 5.5 when in use.
From a different aspect, the present invention provides the following.
(1) A method of inhibiting adsorption of terpenoid onto SCL, which comprises adding polyoxyethylene sorbitan ester to an ophthalmic composition which contains a terpenoid and which becomes a liquid upon dissolution when in use.
(2) A method of inhibiting adsorption of terpenoid onto SCL, which comprises adjusting a pH when in use of an ophthalmic composition, which contains a terpenoid and which becomes a liquid upon dissolution when in use, to not less than 5.5.
The ophthalmic composition for SCL of the present invention improves, for example, the wettability of SCL, thereby to inhibit a decrease in the water content of SCL. As a result, it can inhibit a dry feeling and an uncomfortable feeling during wearing SCL and is useful for enhancing the wettability of SCL.
In addition, (1) an ophthalmic composition which contains polyoxyethylene sorbitan ester and which becomes a liquid upon dissolution when in use and (2) an ophthalmic composition which has an adjusted pH of not less than 5.5 and which becomes a liquid upon dissolution when in use, are associated with less concern of irritation to the eye or an adverse influence such as cloudiness of SCL and the like, since adsorption of terpenoid onto SCL is inhibited.
It is preferable that polyoxyethylene sorbitan ester be added to the concentration when in use of 0.01-0.5 (W/v) %, preferably 0.05-0.2 (W/V) %.
Examples of preferable polyoxyethylene sorbitan ester include polysorbate 80, polysorbates 20, 40, 60, 65, 85 and the like.
The inventive composition is adjusted to have a pH when in use of not less than 5.5, preferably not less than 5.5 and not more than 8. In this way, the adsorption of terpenoid onto SCL can be inhibited. When the pH is not less than 5.5, terpenoid is hardly adsorbed onto SCL. When the pH is not less than 8, the composition becomes strongly alkaline and is not preferable as an ophthalmic composition.
The pH is adjusted using a pH adjusting agent. Examples of the pH adjusting agent include hydrochloric acid, citric acid and a salt thereof (sodium citrate, sodium dihydrogencitrate and the like), phosphoric acid and a salt thereof (disodium hydrogenphosphate, potassium dihydrogenphosphate and the like), acetic acid and a salt thereof (sodium acetate, ammonium acetate and the like), tartaric acid and a salt thereof (sodium tartrate and the like), sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogencarbonate, boric acid and a salt thereof (sodium borate) and the like.
The ophthalmic composition for SCL of the present invention can be prepared by adding a terpenoid and a base (e.g., solvent, ointment base and the like), and further adding, according to the dosage form, various additives such as a solubilizer, buffer, isotonicity agent, preservative, stabilizer, thickener, adsorption inhibitor, chelating agent, pH adjusting agent, suspending agent and the like, as appropriate, and following a known method.
Examples of solvent as a base include water (e.g., distilled water, sterile purified water, physiological saline and the like), alcohols (e.g., ethanol, propylene glycol, macrogol, glycerol and the like) and the like.
Examples of solubilizer include polyvinylpyrrolidone, polyethylene glycol, propylene glycol, polyoxyethylene hydrogenated castor oil 60, polyoxyl 40 stearate and the like.
A buffer is used to make the pH of the inventive ophthalmic composition for SCL approximately 5-9, preferably 6-8. For example, used are boric acid or a salt thereof (sodium borate and the like), citric acid or a salt thereof (sodium citrate and the like), tartaric acid or a salt thereof (sodium tartrate and the like), gluconic acid or a salt thereof (sodium gluconate and the like), acetic acid or a salt thereof (sodium acetate and the like), phosphoric acid or a salt thereof (sodium hydrogenphosphate, sodium dihydrogenphosphate and the like), various amino acids and the like or a combination thereof.
The isotonicity agent may be, for example, sorbitol, glucose, mannitol, glycerol, propylene glycol, sodium chloride, potassium chloride and the like.
Examples of preservative include p-hydroxybenzoates, benzalkonium chloride, benzetonium chloride, chlorobutanol, benzyl alcohol, sorbic acid or a salt thereof, chlorhexidine gluconate, sodium dehydroacetate, cethylpyridinium chloride, alkyldiaminoethylglycine hydrochloride and the like.
Examples of stabilizer include ascorbic acid, sodium edetate, cyclodextrin, condensed phosphoric acid or a salt thereof, sulfite, citric acid or a salt thereof and the like.
Examples of thickener include methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium chondroitin sulfate, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol and the like.
Examples of chelating agent include sodium edetate, sodium citrate, condensed phosphoric acid or a salt thereof (condensed sodium phosphate and the like) and the like.
Examples of suspending agent include methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyoxyethylene hydrogenated castor oil 60, polyoxyl 40 stearate, polyethylene glycol, sodium carboxymethylcellulose, polyvinyl alcohol and the like.
As long as the object of the present invention is not impaired, the inventive ophthalmic composition for SCL may further contain an efficacious ingredient such as vitamins (e.g., retinol palmitate, pyridoxine hydrochloride, tocopherol acetate and the like), angiotonic (e.g., naphazoline hydrochloride, tetrahydrozoline hydrochloride and the like), antiinflammatory agent (e.g., dipotassium glycyrrhizinate, sodium azulenesulfonate and the like), and the like as appropriate.
The dose of the ophthalmic composition for SCL of the present invention when used as an eye drop to an adult, which contains a terpenoid as an active ingredient in 0.0001-0.2 (W/V) %, preferably 0.001-0.05 (W/v) %, is preferably 2 or 3 drops per administration which is given 5 or 6 times a day.